Company Introduction & Proprietary Technologies

March 2008 Lisapharma – Confidential

Company Introduction & Proprietary Technologies March 2008 Lisapharma – Confidential

LISAPHARMA at a glance • Fully owned by Italian capital • Family-ruled business from its foundation to today • Manufacturing plant of dosage forms in full GMP compliance, including β-lactam ceph derivatives dedicated line • Driven to technological developments throughout strong liaisons with different university bodies • Operative on the Italian and international markets through a portfolio of proprietary medicines March 2008 Lisapharma – Confidential

Milestones • 1925: Lisapharma is established in Bologna • 1949: HHQQ and plant moved to actual site of Erba (Co) • 1968: first export business to Taiwan • 1970: establishment of international production units in Nicaragua & Costarica • 1993: first manufacturing activity as toll manufacturer with Novartis • 2000: start of phase-out of production of oral solid non-sterile products • 2002: establishment of the j.-v. with Omicron for the manufacture of oral solid non-sterile products March 2008 Lisapharma – Confidential

Key facts & figures • Fully owned Italian manufacturing plant for sterile injection products, non-sterile liquids, semisolids • J.-V. participation in Omicron plant (Italy) for oral solid non-sterile production • 148 total headcounts, out of which 80reps • International customers portfolio of 81 accounts • International sales in 32 different countries worldwide • Intellectual property of 18 patents covering original technologies • Development & RA expenditure up to 5.60% of company revenues March 2008 Lisapharma – Confidential

Goals • To consolidate the presence in the Italian market • To improve the penetration in existing countries outside Italy and to expand to further new markets its business partneriships • To enlarge the toll manufacturing activities for renowned international companies BY……………………….. March 2008 Lisapharma – Confidential

Strategy • In-house development of generic registration dossiers focusing on niche products (injectable class,…) • Partnering and/or tightening strategic alliances allowing the best exploitation of the in-house developed patented technologies (Sucralfate Gel, Dome Matrix™, Patch-non-Patch™, Chimerical Agglomerates™) • Diversification of the product portfolio to include additional non-RX compounds “dedicated” to specialists (food supplements, medical devices,…) • Strengthening the existing collaborations through the proven high standard of quality and service provided, by doing so attracting new potential customers too March 2008 Lisapharma – Confidential

PROPRIETARY TECHNOLOGIES March 2008 Lisapharma – Confidential

Proprietary technologies • Long-lasting cooperation between Lisapharma and well reputable Universities in Italy • Focusing in the development of novel delivery systems, due to the increased market demand for drug delivery technology • Aiming to develop versatility in drug delivery, as much as adaptability to different drugs to inhance patient compliance ALL THIS LED TO March 2008 Lisapharma – Confidential

Proprietary technologies • Dome Matrix™, oral platform • Patch-non-Patch™, transdermal platform • Chimerical Agglomerates™, inhalation nasal platform • Sucralfate Gel, as unti-ulcer for GI tract and skin wounds FOUR PLATFORMS The technologies are covered by patents and available for discussions March 2008 Lisapharma – Confidential

The Platform Concept in DDS • More than 15% of the total pharma market – in excess of U$ 80 billion - is covered by drug delivery technolgies • Future belongs to biotech drugs, to old drugs to be revaluated, to new drugs offered with appropriate dds, and to generics • The systems invented shall posses not only versatility in delivery, but also adaptability to different drugs • The term platform indicates a delivery system capable to be adapted to various drugs, strenghts, mechanisms of delivery, in order to control not only the time but also the site of delivery March 2008 Lisapharma – Confidential

DOME MATRIX® March 2008 Lisapharma – Confidential

Dome Matrix® • The system is based on tablets (modules) with a peculiar shape made of swellable polymer for controlling the release rate • The typical shape of the module is a cylindrical tablet having one concave and one convex base designed to allow the convex base to be inserted in the concave • The shape permits to put together several modules to create different assembled release systems March 2008 Lisapharma – Confidential

Dome Matrix® March 2008 Lisapharma – Confidential

Dome Matrix® • A peculiar assembly can be obtained by fitting the concave base of two modules allowing the construction of a floating system able to keep the release of the substance into the stomach March 2008 Lisapharma – Confidential

Dome Matrix® • Piled configurations can be obtained by staking the modules convex face into concave face March 2008 Lisapharma – Confidential

Dome Matrix® • Dome Matrix® finds its ideal application whenever there is a need for: • a prolonged release of solid dosage forms and it may represent an effective answer to the need to have versatility in the substance release kinetics • modulation of dose administered • association of different substances in one modular system • improving the efficacy of the substance delivered, providing a time-and-space controlled release system March 2008 Lisapharma – Confidential

Dome Matrix® • Dome Matrix® technology can be applied • To “old” products presented in innovative dosage forms • New compounds combined with an original and innovative delivery route • Dome Matrix® industrial development is in progress • Dome Matrix® is covered by patent, license or transfer could be considered March 2008 Lisapharma – Confidential

Patch-non-Patch® March 2008 Lisapharma – Confidential

Patch-non-Patch® Patches vs. Traditional Systemic Formulations • Constant plasma levels • Lower incidence of side effects vs Injection vs Oral Non invasive Increased bioavailability More acceptable Reduced dosing frequency No need of specialized No drug interaction personnel • Limitation Low skin permeability (daily dosing < 10 mg) March 2008 Lisapharma – Confidential

Patch-non-Patch® Patches vs. Traditional Systemic Formulations • Topical formulations(solutions, creams, gels,…)can: • Be accidentally removed – contact time • Applied at the wrong dose • Stick to cloths • Patches guarantee control in: • Dose applied • Area of application • Contact time • Release kinetics March 2008 Lisapharma – Confidential

Backing Deposit Membrane Adhesive Liner Minitran® Patch-non-Patch® The Typical Structure of a Patch • Multi-layer structures composed of: • Backing • Deposit of the active (solid/liquid) • (Membrane) • Adhesive • Release liner March 2008 Lisapharma – Confidential

Lidoderm® Medicell Patch® Patch-non-Patch® The Typical Structure of a Patch • Plasters • Backing (woven-non-woven) • Thick adhesive hydrogel containing the active • Liner • Gauzes soaked in gel/oil formulations March 2008 Lisapharma – Confidential

SEM Image Patch-non-Patch®: the Novelty Patch-non-Patch® March 2008 Lisapharma – Confidential

Patch-non-Patch®: Characteristics • Dry • Not self-adhesive • Flexible, transparent • Water permeable • Electrically conductive • Organic solvents not required • Adhesive only on wet skin • Washeable with water March 2008 Lisapharma – Confidential

Patch-non-Patch® March 2008 Lisapharma – Confidential

Patch-non-Patch®: Case Studies Lidocaine Estradiol Hydrocortisone Caffeine Nitroglycerin Herbal extracts Thiocolchicoside Progesterone Rutin derivatives Ibuprofen lysine Nicotine&Bupropion Ketoconazole Diclofenac Sumatripan Clindamycin Acyclovir Clorexidine Nicotinamide&Salicylic ac. Thyroxine March 2008 Lisapharma – Confidential

Patch-non-Patch®: Production • Solution (suspension) of all components in water • Lamination on the release liner at predetermined time • Oven drying (60-80°C) • Cutting • Thickness of 40-200 µm • Different shapes/patterns possible March 2008 Lisapharma – Confidential

Patch-non-Patch®: The Cosmetic difference March 2008 Lisapharma – Confidential

Patch-non-Patch®: The Cosmetic advantage March 2008 Lisapharma – Confidential

Patch-non-Patch®: Advantages vs Competitors Feature P-n-P® Patch Plaster Gel % of active released High Low LowLow Time lag No Yes YesNo Duration of activity Long Long LongShort Adaptation to skin surf. Yes No No? Occlusive No Yes Yes/NoNo Water soluble Yes No ?Yes Electrically conductive Yes No ?Yes/No Cosmetically acceptable Yes Yes/No No? Easy to be removed Yes No Yes/NoYes March 2008 Lisapharma – Confidential

Patch-non-Patch®: Advantages vs Competitors Feature P-n-P® Patch PlasterGel Preservatives needed No No YesYes Organic solvents requ. No Yes Yes/NoNo Drying step critical No Yes Yes- Active crystalliz.critical No Yes YesYes Cost of production ++ ++++ +++++ March 2008 Lisapharma – Confidential

Patch-non-Patch ® • Patch-non-Patch® is meant for pharmaceutical, cosmetic, medical device and medical industries • Patch-non-Patch® feasibility studies with different actives/prototypes are available and further can be added • Patch-non-Patch ®allows several potential applications including smoking cessation products, analgesic patches, caffeine-based cellulite treatments, among the others • Patch-non-Patch ®is covered by patent, license or transfer can be considered March 2008 Lisapharma – Confidential

Chimerical Agglomerates™ March 2008 Lisapharma – Confidential

Chimerical Agglomerates™ • Inhalation nasal platform • A new nasal form as powder able to satisfy different technological requirements related to preparation and administration of powders through non-invasive routes such as oral, buccal and nasal ones • The powder is made of agglomerates of micro-particles obtained by spray-drying process of an aqueous or hydro-alcoholic solution containing the substance and excipients March 2008 Lisapharma – Confidential

Chimerical Agglomerates™ • In case of insufflation, the agglomerates dimension are useful for the dose metering of the powder into the insufflation device • After insufflation, due to turbolence of air flow, agglomerates are broken into fragments of appropriate dimension for nasal or buccal administration which are rapidly deaggreagated in the primary micro-particles by water March 2008 Lisapharma – Confidential

Chimerical Agglomerates™ March 2008 Lisapharma – Confidential

Chimerical Agglomerates™ • Chimerical Agglomerates™ is very versatile system since it is possible to prepare formulations of different substances by varying the composition of the micro-particles • Chimerical Agglomerates™ scale of development is laboratory tested – scale up phase • Chimerical Agglomerates™ is covered by patent, license or transfer could be considered March 2008 Lisapharma – Confidential

Chimerical Agglomerates™ • Highly respirable insulin case study • Dry insulin powders have been prepared by using spray-drying process starting from suspensions or aqueous solutions of the active ingredient in acetic acid • As metering device has been used a commercial device able to administer 2 mg of insulin powder when activated by an air flow of 60 l/min • Stability study has been carried out for 12 months during which the powders have been kept in two different conditions: 25°C-60% RU and 2-8°C March 2008 Lisapharma – Confidential

Chimerical Agglomerates™ • Highly respirable insulin case study • Powders obtained form insulin suspensions showed lower values of FPF (10-30%) compared to those obtained by drying of solutions of insulin (60-80%) • Particles obtained applying this latter option have corrugated surface characteristics, when examined through SEM analysis • All powders showed a median volume diameter below 5 µm, therefore suitable for inhalatory administration • The chemical and physical stabilities of powders obtained starting from acetic acid solutions were the best one and the hydrolytic degradation products, the related substances as well as the covalent aggregation products remain within the spec limits described in EP, also when the powders were stored at 25°C up to 24 months March 2008 Lisapharma – Confidential

Chimerical Agglomerates™ • Highly respirable insulin case study • By spray-drying process therefore is possible to obtain dry insulin powders characterized by high stability and suitable particle shape able to make the powders highly breathable and manageable for manufacturing • These powders show good flow properties which allow them to be easily charged in a adevice for insufflation • By this approach insulin crystals are transformed in micro-particles • The product does not contain excipients, so reducing the potential side effects associated to them • The room temperature stability of these pwders allows the product to be stored in non-refrigerated conditions March 2008 Lisapharma – Confidential

Sucralfate Gel March 2008 Lisapharma – Confidential

Sucralfate Gel • Sucralfate is a safe and active antiulcer drug • A new physical form of Sucralfate, named Sucralfate Gel, has been patented and developed and possesses colloidal properties due to the reduced particle size • The material is a humid solid since the drying of the sucralfate gel causes the lost of the gel properties • It has been demonstrated that sucralfate gel superior activity is due to a demonstrated strong bio-adhesion towards the oral and gastrointestinal mucosa, which allows the product to persist in contact with the tissue to be healed March 2008 Lisapharma – Confidential

Sucralfate Gel • Other than the development of Sucralfate Gel as oral suspension for the treatment of GI ulcers, the peculiarity of this new material has suggested a series of further development. • One of this has been the topical use of Sucralfate Gel for the treatment of the skin ulcers of various origin, which has got the CE approval as Medical Device • This was made possible again by the bio-adhesion properties of the Sucralfate humid gel that allowed the preparation of a simplified and self-adherent topical preparation • The topical preparation can be used also as a carrier for topical substances and it is patented March 2008 Lisapharma – Confidential

Sucralfate Gel March 2008 Lisapharma – Confidential

Sucralfate Gel • There are already on the market in many countries various products based on the Sucralfate Gel technology including: • Sucralfate gel topical 25% for the treatment of skin ulcers of various origin (Medical Device) • Sucralfate gel oral suspension 1g/5ml sachet • Sucralfate gel oral suspension 2g/10ml sachet • Dried sucralfate gel tablets 1g (under registration) • Dried sucralfate gel sequential tablets + ketoprofen • Dried Sucralfate gel sequential tablets + aspirin March 2008 Lisapharma – Confidential

…Good tips to partnering with Lisapharma • Small though efficient and dedicated team group allowing quick decision process • Flexibility combined to first class service • Quick adaptation to market changes • Fast reacting to customers’ demands and needs • Commitment to innovation • Very promising tech package portfolio • Excellent expertise and know how in manufacturing of injection products • Independent company not belonging to any group March 2008 Lisapharma – Confidential

Company Introduction & Proprietary Technologies